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P00636 (F16P1_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fructose-1,6-bisphosphatase 1

Short name=FBPase 1
EC=3.1.3.11
Alternative name(s):
D-fructose-1,6-bisphosphate 1-phosphohydrolase 1
Liver FBPase
Gene names
Name:FBP1
Synonyms:FBP
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length338 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain By similarity.

Catalytic activity

D-fructose 1,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.

Cofactor

Binds 3 magnesium ions per subunit.

Enzyme regulation

Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects.

Pathway

Carbohydrate biosynthesis; gluconeogenesis.

Subunit structure

Homotetramer.

Miscellaneous

The molecule has a highly reactive cysteine residue (Cys-117 or Cys-129), which tends to form mixed disulfides (e.g. with homocystine) but is not essential for enzyme activity.

Sequence similarities

Belongs to the FBPase class 1 family.

Biophysicochemical properties

Kinetic parameters:

KM=1.2 µM for fructose-1,6-diphosphate

Ontologies

Keywords
   Biological processCarbohydrate metabolism
Gluconeogenesis
   LigandMagnesium
Metal-binding
   Molecular functionHydrolase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to drug

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to magnesium ion

Inferred from sequence or structural similarity. Source: UniProtKB

dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

fructose 6-phosphate metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of Ras protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of glycolytic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein homotetramerization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionAMP binding

Inferred from sequence or structural similarity. Source: UniProtKB

fructose 1,6-bisphosphate 1-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

monosaccharide binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2
Chain2 – 338337Fructose-1,6-bisphosphatase 1
PRO_0000200500

Regions

Nucleotide binding18 – 225AMP
Nucleotide binding28 – 325AMP
Nucleotide binding113 – 1142AMP
Region122 – 1254Substrate binding
Region213 – 2164Substrate binding
Region244 – 2496Substrate binding
Region275 – 2773Substrate binding

Sites

Metal binding691Magnesium 1
Metal binding981Magnesium 1
Metal binding981Magnesium 2
Metal binding1191Magnesium 2
Metal binding1191Magnesium 3
Metal binding1211Magnesium 2; via carbonyl oxygen
Metal binding1221Magnesium 3
Metal binding2811Magnesium 3
Binding site1411AMP
Binding site2651Substrate

Amino acid modifications

Modified residue21N-acetylthreonine
Modified residue1511N6-succinyllysine By similarity
Modified residue2081Phosphoserine; by PKA

Experimental info

Mutagenesis551A → L: Destabilizes the inactive T-state and promotes transition to the R-state.
Sequence conflict21T → A AA sequence Ref.3
Sequence conflict41Q → E AA sequence Ref.3
Sequence conflict211E → Q AA sequence Ref.2
Sequence conflict971S → T AA sequence Ref.2
Sequence conflict1571G → E AA sequence Ref.2
Sequence conflict2001D → N AA sequence Ref.2
Sequence conflict2291Q → E AA sequence Ref.2

Secondary structure

..................................................................... 338
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00636 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 610BF8D3C6D320F6

FASTA33836,779
        10         20         30         40         50         60 
MTDQAAFDTN IVTLTRFVME EGRKARGTGE MTQLLNSLCT AVKAISTAVR KAGIAHLYGI 

        70         80         90        100        110        120 
AGSTNVTGDQ VKKLDVLSND LVINVLKSSF ATCVLVSEED KNAIIVEPEK RGKYVVCFDP 

       130        140        150        160        170        180 
LDGSSNIDCL VSIGTIFGIY RKNSTDEPSE KDALQPGRNL VAAGYALYGS ATMLVLAMVN 

       190        200        210        220        230        240 
GVNCFMLDPA IGEFILVDRD VKIKKKGSIY SINEGYAKEF DPAITEYIQR KKFPPDNSAP 

       250        260        270        280        290        300 
YGARYVGSMV ADVHRTLVYG GIFMYPANKK SPKGKLRLLY ECNPMAYVME KAGGLATTGK 

       310        320        330 
EAVLDIVPTD IHQRAPIILG SPEDVTELLE IYQKHAAK 

« Hide

References

[1]"Isolation and sequence analysis of the cDNA for pig kidney fructose 1,6-bisphosphatase."
Williams M.K., Kantrowitz E.R.
Proc. Natl. Acad. Sci. U.S.A. 89:3080-3082(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[2]"Complete amino acid sequence of pig kidney fructose-1,6-bisphosphatase."
Marcus F., Edelstein I., Reardon I., Heinrikson R.L.
Proc. Natl. Acad. Sci. U.S.A. 79:7161-7165(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-336, ACETYLATION AT THR-2, PHOSPHORYLATION AT SER-208.
Tissue: Kidney cortex.
[3]"Conservation of primary structure at the proteinase-sensitive site of fructose 1,6-bisphosphatases."
McGregor J.S., Hannappel E., Xu G.-J., Pontremoli S., Horecker B.L.
Arch. Biochem. Biophys. 217:652-664(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-24 AND 44-61, ACETYLATION AT THR-2.
Tissue: Kidney.
[4]"Mechanism of action of fructose 1,6-bisphosphatase."
Benkovic S.J., Demaine M.M.
Adv. Enzymol. Relat. Areas Mol. Biol. 53:45-82(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE-BINDING SITE, LIGANDS, REVIEW.
[5]"Structure refinement of fructose-1,6-bisphosphatase and its fructose 2,6-bisphosphate complex at 2.8-A resolution."
Ke H.M., Thorpe C.M., Seaton B.A., Lipscomb W.N., Marcus F.
J. Mol. Biol. 212:513-539(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-2,6-BISPHOSPHATE, SEQUENCE REVISION.
[6]"Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 6-phosphate, AMP, and magnesium."
Ke H.M., Zhang Y.P., Lipscomb W.N.
Proc. Natl. Acad. Sci. U.S.A. 87:5243-5247(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-6-PHOSPHATE; AMP AND MAGNESIUM, ENZYME REGULATION, SUBUNIT.
[7]"Crystal structure of the neutral form of fructose-1,6-bisphosphatase complexed with the product fructose 6-phosphate at 2.1-A resolution."
Ke H.M., Zhang Y.P., Liang J.-Y., Lipscomb W.N.
Proc. Natl. Acad. Sci. U.S.A. 88:2989-2993(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-6-PHOSPHATE.
[8]"Crystal structure of the neutral form of fructose 1,6-bisphosphatase complexed with regulatory inhibitor fructose 2,6-bisphosphate at 2.6-A resolution."
Liang J.-Y., Huang S., Zhang Y.P., Ke H.M., Lipscomb W.N.
Proc. Natl. Acad. Sci. U.S.A. 89:2404-2408(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH FRUCTOSE-2,6-BISPHOSPHATE.
[9]"Role of a dynamic loop in cation activation and allosteric regulation of recombinant porcine fructose-1,6-bisphosphatase."
Choe J.-Y., Poland B.W., Fromm H.J., Honzatko R.B.
Biochemistry 37:11441-11450(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) IN COMPLEX WITH ZINC IONS, COFACTOR, ENZYME REGULATION.
[10]"Crystal structures of fructose 1,6-bisphosphatase: mechanism of catalysis and allosteric inhibition revealed in product complexes."
Choe J.-Y., Fromm H.J., Honzatko R.B.
Biochemistry 39:8565-8574(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) IN COMPLEXES WITH FRUCTOSE-6-PHOSPHATE; PHOSPHATE; AMP; MAGNESIUM AND ZINC IONS, SUBUNIT, ENZYME REGULATION.
[11]"Metaphosphate in the active site of fructose-1,6-bisphosphatase."
Choe J.-Y., Iancu C.V., Fromm H.J., Honzatko R.B.
J. Biol. Chem. 278:16015-16020(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM IONS; FRUCTOSE-6-PHOSPHATE AND PHOSPHATE, COFACTOR, ENZYME MECHANISM.
[12]"Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors."
Choe J.-Y., Nelson S.W., Arienti K.L., Axe F.U., Collins T.L., Jones T.K., Kimmich R.D.A., Newman M.J., Norvell K., Ripka W.C., Romano S.J., Short K.M., Slee D.H., Fromm H.J., Honzatko R.B.
J. Biol. Chem. 278:51176-51183(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH THE SYNTHETIC INHIBITOR OC252; FRUCTOSE-6-PHOSPHATE; PHOSPHATE AND DIVALENT METAL CATIONS, COFACTOR, SUBUNIT, ENZYME REGULATION.
[13]"R-state AMP complex reveals initial steps of the quaternary transition of fructose-1,6-bisphosphatase."
Iancu C.V., Mukund S., Fromm H.J., Honzatko R.B.
J. Biol. Chem. 280:19737-19745(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF MUTANT LEU-55 IN COMPLEXES WITH AMP; FRUCTORSE-6-PHOSPHAT; PHOSPHATE AND MAGNESIUM IONS, SUBUNIT, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[14]"Structures of mammalian and bacterial fructose-1,6-bisphosphatase reveal the basis for synergism in AMP/fructose 2,6-bisphosphate inhibition."
Hines J.K., Chen X., Nix J.C., Fromm H.J., Honzatko R.B.
J. Biol. Chem. 282:36121-36131(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM IONS AND FRUCTOSE-2,6-DIPHOSPHATE, SUBUNIT, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M86347 mRNA. Translation: AAA31035.1.
PIRPAPGF. S37696.
RefSeqNP_999144.1. NM_213979.1.
UniGeneSsc.5127.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CNQX-ray2.27A2-338[»]
1EYIX-ray2.32A2-338[»]
1EYJX-ray2.28A/B2-338[»]
1EYKX-ray2.23A/B2-338[»]
1FBCX-ray2.60A/B2-336[»]
1FBDX-ray2.90A/B2-336[»]
1FBEX-ray3.00A/B2-336[»]
1FBFX-ray2.70A/B2-336[»]
1FBGX-ray3.00A/B2-336[»]
1FBHX-ray2.50A/B2-336[»]
1FBPX-ray2.50A/B2-336[»]
1FJ6X-ray2.50A2-338[»]
1FJ9X-ray2.50A/B2-338[»]
1FPBX-ray2.60A/B2-336[»]
1FPDX-ray2.10A/B2-336[»]
1FPEX-ray2.20A/B2-336[»]
1FPFX-ray2.10A/B2-336[»]
1FPGX-ray2.30A/B2-336[»]
1FPIX-ray2.30A/B2-336[»]
1FPJX-ray2.20A/B2-336[»]
1FPKX-ray3.00A/B2-336[»]
1FPLX-ray2.30A/B2-336[»]
1FRPX-ray2.00A/B2-336[»]
1FSAX-ray2.30A/B2-338[»]
1KZ8X-ray2.00A/F2-338[»]
1LEVX-ray2.15A/F2-338[»]
1NUWX-ray1.30A2-338[»]
1NUXX-ray1.60A2-338[»]
1NUYX-ray1.30A2-338[»]
1NUZX-ray1.90A2-338[»]
1NV0X-ray1.80A2-338[»]
1NV1X-ray1.90A2-338[»]
1NV2X-ray2.10A2-338[»]
1NV3X-ray2.00A2-338[»]
1NV4X-ray1.90A2-338[»]
1NV5X-ray1.90A2-338[»]
1NV6X-ray2.15A2-338[»]
1NV7X-ray2.15A/B2-338[»]
1Q9DX-ray2.35A/B2-338[»]
1RDXX-ray2.75A/B2-338[»]
1RDYX-ray2.20A/B2-338[»]
1RDZX-ray2.05A/B2-338[»]
1YXIX-ray2.00A2-338[»]
1YYZX-ray1.85A2-338[»]
1YZ0X-ray2.07A/B2-338[»]
2F3BX-ray1.80A1-338[»]
2F3DX-ray1.83A1-338[»]
2FBPX-ray2.80A/B2-336[»]
2QVUX-ray1.50A/B2-338[»]
2QVVX-ray2.03A/B2-338[»]
3FBPX-ray2.80A/B2-336[»]
4FBPX-ray2.50A/B/C/D2-336[»]
4GBVX-ray2.90A2-336[»]
4GBWX-ray2.00A2-336[»]
4GWSX-ray2.75A/B2-338[»]
4GWUX-ray3.00A2-338[»]
4GWWX-ray3.20A2-338[»]
4GWXX-ray2.35A2-338[»]
4GWYX-ray3.00A2-338[»]
4GWZX-ray2.60A/B2-338[»]
4GX3X-ray2.25A/B2-338[»]
4GX4X-ray2.50A/B2-338[»]
4GX6X-ray2.50A/B2-338[»]
4H45X-ray3.10A2-338[»]
4H46X-ray2.50A2-338[»]
4KXPX-ray2.70A/B1-338[»]
5FBPX-ray2.10A/B2-336[»]
ProteinModelPortalP00636.
SMRP00636. Positions 7-338.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP00636.
ChEMBLCHEMBL2263.
DrugBankDB00131. Adenosine monophosphate.

Proteomic databases

PaxDbP00636.
PRIDEP00636.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID397038.
KEGGssc:397038.

Organism-specific databases

CTD2203.

Phylogenomic databases

eggNOGCOG0158.
HOGENOMHOG000191265.
HOVERGENHBG005627.
KOK03841.

Enzyme and pathway databases

BRENDA3.1.3.11. 6170.
SABIO-RKP00636.
UniPathwayUPA00138.

Family and domain databases

HAMAPMF_01855. FBPase_class1.
InterProIPR000146. FBPase_class-1/SBPase.
IPR028343. FBPtase.
IPR020548. Fructose_bisphosphatase_AS.
[Graphical view]
PANTHERPTHR11556. PTHR11556. 1 hit.
PfamPF00316. FBPase. 1 hit.
[Graphical view]
PIRSFPIRSF500210. FBPtase. 1 hit.
PIRSF000904. FBPtase_SBPase. 1 hit.
PRINTSPR00115. F16BPHPHTASE.
PROSITEPS00124. FBPASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00636.

Entry information

Entry nameF16P1_PIG
AccessionPrimary (citable) accession number: P00636
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 133 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways